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A Transcriptomic Severity Classifier IMX-SEV-3b to Predict Mortality in Intensive Care Unit Patients with COVID-19: A Prospective Observational Pilot Study

The prediction of disease outcomes in COVID-19 patients in the ICU is of critical importance, and the examination of host gene expressions is a promising tool. The 29-host mRNA Inflam-matix-Severity-3b (IMX-SEV-3b) classifier has been reported to predict mortality in emergency department COVID-19 pa...

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Autores principales: Daenen, Katrijn, Tong-Minh, Kirby, Liesenfeld, Oliver, Stoof, Sara C. M., Huijben, Jilske A., Dalm, Virgil A. S. H., Gommers, Diederik, van Gorp, Eric C. M., Endeman, Henrik
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10573111/
https://www.ncbi.nlm.nih.gov/pubmed/37834841
http://dx.doi.org/10.3390/jcm12196197
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author Daenen, Katrijn
Tong-Minh, Kirby
Liesenfeld, Oliver
Stoof, Sara C. M.
Huijben, Jilske A.
Dalm, Virgil A. S. H.
Gommers, Diederik
van Gorp, Eric C. M.
Endeman, Henrik
author_facet Daenen, Katrijn
Tong-Minh, Kirby
Liesenfeld, Oliver
Stoof, Sara C. M.
Huijben, Jilske A.
Dalm, Virgil A. S. H.
Gommers, Diederik
van Gorp, Eric C. M.
Endeman, Henrik
author_sort Daenen, Katrijn
collection PubMed
description The prediction of disease outcomes in COVID-19 patients in the ICU is of critical importance, and the examination of host gene expressions is a promising tool. The 29-host mRNA Inflam-matix-Severity-3b (IMX-SEV-3b) classifier has been reported to predict mortality in emergency department COVID-19 patients and surgical ICU patients. The accuracy of the IMX-SEV-3b in predicting mortality in COVID-19 patients admitted to the ICU is yet unknown. Our aim was to investigate the accuracy of the IMX-SEV-3b in predicting the ICU mortality of COVID-19 patients. In addition, we assessed the predictive performance of routinely measured biomarkers and the Sequential Organ Failure Assessment (SOFA) score as well. This was a prospective observational study enrolling COVID-19 patients who received mechanical ventilation on the ICU of the Erasmus MC, the Netherlands. The IMX-SEV-3b scores were generated by amplifying 29 host response genes from blood collected in PAXgene(®) Blood RNA tubes. A severity score was provided, ranging from 0 to 1 for increasing disease severity. The primary outcome was the accuracy of the IMX-SEV-3b in predicting ICU mortality, and we calculated the AUROC of the IMX-SEV-3b score, the biomarkers C-reactive protein (CRP), D-dimer, ferritin, leukocyte count, interleukin-6 (IL-6), lactate dehydrogenase (LDH), neutrophil-to-lymphocyte ratio (NLR), procalcitonin (PCT) and the SOFA score. A total of 53 patients were included between 1 March and 30 April 2020, with 47 of them being included within 72 h of their admission to the ICU. Of these, 18 (34%) patients died during their ICU stay, and the IMX-SEV-3b scores were significantly higher in non-survivors compared to survivors (0.65 versus 0.57, p = 0.05). The Area Under the Receiver Operating Characteristic Curve (AUROC) for prediction of ICU mortality by the IMX-SEV-3b was 0.65 (0.48–0.82). The AUROCs of the biomarkers ranged from 0.52 to 0.66, and the SOFA score had an AUROC of 0.81 (0.69–0.93). The AUROC of the pooled biomarkers CRP, D-dimer, ferritin, leukocyte count, IL-6, LDH, NLR and PCT for prediction of ICU mortality was 0.81 (IQR 0.69–0.93). Further validation in a larger interventional trial of a point-of-care version of the IMX-SEV-3b classifier is warranted to determine its value for patient management.
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spelling pubmed-105731112023-10-14 A Transcriptomic Severity Classifier IMX-SEV-3b to Predict Mortality in Intensive Care Unit Patients with COVID-19: A Prospective Observational Pilot Study Daenen, Katrijn Tong-Minh, Kirby Liesenfeld, Oliver Stoof, Sara C. M. Huijben, Jilske A. Dalm, Virgil A. S. H. Gommers, Diederik van Gorp, Eric C. M. Endeman, Henrik J Clin Med Article The prediction of disease outcomes in COVID-19 patients in the ICU is of critical importance, and the examination of host gene expressions is a promising tool. The 29-host mRNA Inflam-matix-Severity-3b (IMX-SEV-3b) classifier has been reported to predict mortality in emergency department COVID-19 patients and surgical ICU patients. The accuracy of the IMX-SEV-3b in predicting mortality in COVID-19 patients admitted to the ICU is yet unknown. Our aim was to investigate the accuracy of the IMX-SEV-3b in predicting the ICU mortality of COVID-19 patients. In addition, we assessed the predictive performance of routinely measured biomarkers and the Sequential Organ Failure Assessment (SOFA) score as well. This was a prospective observational study enrolling COVID-19 patients who received mechanical ventilation on the ICU of the Erasmus MC, the Netherlands. The IMX-SEV-3b scores were generated by amplifying 29 host response genes from blood collected in PAXgene(®) Blood RNA tubes. A severity score was provided, ranging from 0 to 1 for increasing disease severity. The primary outcome was the accuracy of the IMX-SEV-3b in predicting ICU mortality, and we calculated the AUROC of the IMX-SEV-3b score, the biomarkers C-reactive protein (CRP), D-dimer, ferritin, leukocyte count, interleukin-6 (IL-6), lactate dehydrogenase (LDH), neutrophil-to-lymphocyte ratio (NLR), procalcitonin (PCT) and the SOFA score. A total of 53 patients were included between 1 March and 30 April 2020, with 47 of them being included within 72 h of their admission to the ICU. Of these, 18 (34%) patients died during their ICU stay, and the IMX-SEV-3b scores were significantly higher in non-survivors compared to survivors (0.65 versus 0.57, p = 0.05). The Area Under the Receiver Operating Characteristic Curve (AUROC) for prediction of ICU mortality by the IMX-SEV-3b was 0.65 (0.48–0.82). The AUROCs of the biomarkers ranged from 0.52 to 0.66, and the SOFA score had an AUROC of 0.81 (0.69–0.93). The AUROC of the pooled biomarkers CRP, D-dimer, ferritin, leukocyte count, IL-6, LDH, NLR and PCT for prediction of ICU mortality was 0.81 (IQR 0.69–0.93). Further validation in a larger interventional trial of a point-of-care version of the IMX-SEV-3b classifier is warranted to determine its value for patient management. MDPI 2023-09-26 /pmc/articles/PMC10573111/ /pubmed/37834841 http://dx.doi.org/10.3390/jcm12196197 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Daenen, Katrijn
Tong-Minh, Kirby
Liesenfeld, Oliver
Stoof, Sara C. M.
Huijben, Jilske A.
Dalm, Virgil A. S. H.
Gommers, Diederik
van Gorp, Eric C. M.
Endeman, Henrik
A Transcriptomic Severity Classifier IMX-SEV-3b to Predict Mortality in Intensive Care Unit Patients with COVID-19: A Prospective Observational Pilot Study
title A Transcriptomic Severity Classifier IMX-SEV-3b to Predict Mortality in Intensive Care Unit Patients with COVID-19: A Prospective Observational Pilot Study
title_full A Transcriptomic Severity Classifier IMX-SEV-3b to Predict Mortality in Intensive Care Unit Patients with COVID-19: A Prospective Observational Pilot Study
title_fullStr A Transcriptomic Severity Classifier IMX-SEV-3b to Predict Mortality in Intensive Care Unit Patients with COVID-19: A Prospective Observational Pilot Study
title_full_unstemmed A Transcriptomic Severity Classifier IMX-SEV-3b to Predict Mortality in Intensive Care Unit Patients with COVID-19: A Prospective Observational Pilot Study
title_short A Transcriptomic Severity Classifier IMX-SEV-3b to Predict Mortality in Intensive Care Unit Patients with COVID-19: A Prospective Observational Pilot Study
title_sort transcriptomic severity classifier imx-sev-3b to predict mortality in intensive care unit patients with covid-19: a prospective observational pilot study
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10573111/
https://www.ncbi.nlm.nih.gov/pubmed/37834841
http://dx.doi.org/10.3390/jcm12196197
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